Risk Y-haplotypes and pathogenic variants of Arab-ancestry boys with autism by an exome-wide association study
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ORIGINAL ARTICLE
Risk Y-haplotypes and pathogenic variants of Arab-ancestry boys with autism by an exome-wide association study Laila M. Alsubaie1,2 · Hind Saleh Alsuwat1 · Noor B Almandil3 · Abdulla AlSulaiman4 · Sayed AbdulAzeez1 · J. Francis Borgio1 Received: 6 May 2020 / Accepted: 7 September 2020 © Springer Nature B.V. 2020
Abstract Autism is heterogeneous multifactorial neurodevelopmental and neuropsychiatric disorder with repetitive and limited behaviors as well as communication deficits. Prevalence of autism in males is predominant than females, but their genetic association is unclear. The study was performed to investigate Y-chromosome haplotypes, significant risk variants and susceptibility genes associated with autistic Saudi young males with autism. Exome genotyping microarray analysis was performed in Saudi young boys with autism (cases, n = 47) and without autism and other genetic or neurodevelopmental disorders (control, n = 43) to identify the functional exonic risk variations among 243,345 exonic variations. The most significant single nucleotide polymorphisms (SNPs) of protein coding associated with autism in Saudi young boys were studied for functional enrichment. Y-chromosome haplotyping analysis of 6 SNPs such as rs1865680, rs2032624, rs2032658, rs2032631, rs9786153 and rs13447352 uncovered the most significant protective (ACGACAp = 2.94 × 10−9) among the controls and the high risk Y-haplotype (GAAGTC p = 6.85 × 10−6) among autistic boys. Exome association study revealed 6 susceptible genes, MCC, AUTS2, VSX1, SETBP1, CNTN3, and PCDH11Y that were known for autistic disorder. The significant predisposed genes with functional variants of Y-chromomere are strongly connected with spermatogenic failure (p = 8.02 × 10−8), azoospermia (p = 6.32 × 10−7), partial chromosome Y deletion (p = 7.66 × 10−6), HDMs demethylate histones pathway (p = 3.55 × 10−4) and immune system diseases (p = 4.11 × 10−3). Y-haplotypes and highly significant pathogenic exonic variants in MCC, AUTS2, VSX1, SETBP1, CNTN3 and PCDH11Y genes are more influential genetic factors for developing autism in boys of Arab origin. Keywords Autism spectrum disorder · Haplotype · Boy · Polymorphism · SNPs · Y-chromosome
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05832-6) contains supplementary material, which is available to authorized users. 1
Laila M. Alsubaie [email protected]
Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Corniche Road, Dammam, Saudi Arabia
2
Hind Saleh Alsuwat [email protected]
Department of Biololgy, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
3
Department of Clinical Pharmacy Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
4
Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, S
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